Evidence map›Paper›PMID 31768029›Full record

ArticleNature microbiology2020

Epigenomic characterization of Clostridioides difficile finds a conserved DNA methyltransferase that mediates sporulation and pathogenesis.

Pedro H Oliveira, John W Ribis, Elizabeth M Garrett, Dominika Trzilova, Alex Kim, Ognjen Sekulovic, Edward A Mead, Theodore Pak, Shijia Zhu, Gintaras Deikus and 21 more

Open access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
8.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 115 citations in OpenAlex.

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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 5 institutions in 2 countries.

Pedro H OliveiraDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-3161-8367
John W RibisDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
Elizabeth M GarrettDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Dominika TrzilovaDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Alex KimDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Ognjen SekulovicDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1006-0595
Edward A MeadDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Theodore PakDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Shijia ZhuDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Gintaras DeikusDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Marie TouchonMicrobial Evolutionary Genomics, Institut Pasteur, Paris, France.
Martha Lewis-SandariDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Colleen BeckfordDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Nathalie E ZeitouniDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Deena R AltmanDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-1948-3834
Elizabeth WebsterDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Irina OussenkoDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Supinda BunyavanichDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Aneel K AggarwalDepartment of Pharmacological Sciences and Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY, USA.
Ali BashirDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Gopi PatelDepartment of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY, USA.
Frances WallachDepartment of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY, USA.
Camille HamulaDepartment of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY, USA.
Shirish HuprikarDepartment of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY, USA.
Eric E SchadtDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Robert SebraDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Harm van BakelDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-1376-6916
Andrew KasarskisDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA.
Rita TamayoDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Aimee ShenDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA. aimee.shen@tufts.edu.ORCID http://orcid.org/0000-0002-9786-5742
Gang FangDepartment of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, NY, USA. gang.fang@mssm.edu.ORCID http://orcid.org/0000-0002-2462-9124
Icahn School of Medicine at Mount Sinai · USTufts University · USUniversity of North Carolina at Chapel Hill · USCentre National de la Recherche Scientifique · FRSema4 (United States) · US

Funding

Investigating genomic factors and microbiome features that impact CDI transmission and prognosisR01AI119145 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BASHIR, ALI M, VAN BAKEL, HARM · 2015 to 2019
$4.2M
Spore Assembly in Clostridium DifficileR01AI122232 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI SHEN, AIMEE · 2016 to 2025
$4.2M
MOLECULAR GENETICS OF BASIC CELL FUNCTIONST32GM007310 · NIGMS · TUFTS UNIVERSITY BOSTON · PI CAMILLI, ANDREW · 1987 to 2020
$3.9M
Regulation of Clostridium difficile Colonization FactorsR01AI107029 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TAMAYO, RITA · 2013 to 2022
$3.9M
Structure and Specificity of Restriction-Modification (R-M) SystemsR35GM131780 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ANEEL K. AGGARWAL · 2019 to 2026
$3.4M
Development of a microphysiologic system to assay the interaction of the human colonic epithelium on Clostridium difficileR01DK120606 · NIDDK · UNIVERSITY OF WASHINGTON · PI ALLBRITTON, NANCY L., SHEIKH, SHEHZAD Z. · 2020 to 2023
$2.2M
Methods for Multiscale and Integrative Characterization of Bacterial EpigenomesR01GM114472 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FANG, GANG · 2015 to 2019
$2.1M
Phase variation of virulence factors in Clostridioides difficileR37AI107029 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RITA TAMAYO · 2025 to 2026
$1.0M
Cell Division in ClostridioidesdifficileR37AI122232 · NIAID · TUFTS UNIVERSITY BOSTON · PI Aimee Shen · 2026 to 2026
$509k
NIAID NIH HHS R01 AI107029NIAID NIH HHS R01 AI119145NIAID NIH HHS R37 AI107029NIAID NIH HHS R37 AI122232NIDDK NIH HHS R01 DK120606NIGMS NIH HHS R01 GM114472NIGMS NIH HHS R35 GM131780NIGMS NIH HHS T32 GM007310
6 · The paper itself

Abstract

Clostridioides (formerly Clostridium) difficile is a leading cause of healthcare-associated infections. Although considerable progress has been made in the understanding of its genome, the epigenome of C. difficile and its functional impact has not been systematically explored. Here, we perform a comprehensive DNA methylome analysis of C. difficile using 36 human isolates and observe a high level of epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity, the corresponding gene of which is highly conserved across our dataset and in all of the approximately 300 global C. difficile genomes examined. Inactivation of the methyltransferase gene negatively impacts sporulation, a key step in C. difficile disease transmission, and these results are consistently supported by multiomics data, genetic experiments and a mouse colonization model. Further experimental and transcriptomic analyses suggest that epigenetic regulation is associated with cell length, biofilm formation and host colonization. These findings provide a unique epigenetic dimension to characterize medically relevant biological processes in this important pathogen. This study also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomic studies.

Indexed as

Epigenesis, GeneticAnimalsBacterial ProteinsClostridioides difficileClostridium InfectionsCricetinaeDNA, BacterialDNA MethylationDNA Modification MethylasesEpigenomeGene Expression Regulation, BacterialGenetic VariationGenome, BacterialHumansMiceMutationBacterial ProteinsDNA, BacterialDNA Modification Methylases

Identifiers

PMID31768029
PMCPMC6925328
OpenAlexW2989966661

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.